Conventionally, in a case in which bio-macromolecules that are represented by proteins are separated and purified, generally, porous type particles having a synthetic macromolecule as a matrix, particles having a crosslinked gel of a hydrophilic natural macromolecule as a matrix, and the like are used. An ion exchanger having the porous type synthetic macromolecule as a matrix has an advantage that the volume change caused by salt concentration is small, and in a case in which the ion exchanger is packed in a column and used for chromatography, the pressure resistance at the time of liquid permeation is favorable. However, when this ion exchanger is used for the separation of a protein or the like, non-specific adsorption such as irreversible adsorption based on hydrophobic interaction occurs, and therefore, there is a problem that asymmetrization of peaks occurs, or a protein adsorbed to an ion exchanger by the hydrophobic interaction remains adsorbed and cannot be collected.
Meanwhile, in the case of ion exchangers having crosslinked gels of hydrophilic natural macromolecules, which are represented by polysaccharides such as dextran and agarose as matrices, there is an advantage that non-specific adsorption of proteins hardly occurs. However, these ion exchangers have a defect that the ion exchangers swell conspicuously in aqueous solutions, undergo a large volume change due to the ionic strength of a solution and a large volume change between free acid type and load-sensitive type, and do not have sufficient mechanical strength. Particularly, in the case of using a crosslinked gel in chromatography, the ion exchangers have a defect that there is a high pressure loss at the time of liquid permeation, and the gel is consolidated as a result of liquid permeation.
In order to overcome the defects of crosslinked gels of hydrophilic natural macromolecules, attempts have been hitherto made to combine the crosslinked gels with rigid substances that serve as a so-called “skeleton”.
For example, it is disclosed in Patent Literature 1 that when a composite in which a gel such as a natural macromolecule gel is retained within pores of a porous macromolecule is used in the field of peptide synthesis, the load factors of reactive substances can be increased, and synthesis can be achieved with high yield.
Furthermore, in Patent Literature 1, since a hard synthetic macromolecule substance is surrounded by a gel, an effect is described that even if the composite is used in the form of a column bed, there is no change in volume, and the pressure of the flow-through that permeates through the column does not change.
In Patent Literatures 2 and 3, separation materials in which a xerogel of a polysaccharide such as dextran or cellulose is retained in an inorganic porous body such as celite, are disclosed. This gel is provided with a diethylaminoethyl (DEAE) group or the like in order to add sorption performance, and the gel is used for the removal of hemoglobin. As an effect thereof, satisfactory liquid permeability in columns is mentioned.
In Patent Literature 4, an ion exchanger of a hybrid copolymer, in which pores of a copolymer having a macro network structure are filled with a crosslinked copolymer gel synthesized from monomers, is disclosed. A crosslinked copolymer gel has problems with pressure loss, volume change and the like in the case of having a low degree of crosslinking; however, it is described that by employing a hybrid copolymer, the liquid permeation characteristics are improved so that the pressure loss is decreased, and that the ion exchange capacity is increased while the leakage behavior is improved.
Compositized filler materials in which a crosslinked gel of a hydrophilic natural macromolecule having a macro network structure is filled in the pores of an organic synthetic polymer base, have been proposed (see Patent Literatures 5 and 6).
In Patent Literature 7, synthesis of porous particles formed by copolymerization of glycidyl methacrylate and an acrylic crosslinking monomer is disclosed.